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Q02956

- KPCZ_MOUSE

UniProt

Q02956 - KPCZ_MOUSE

Protein

Protein kinase C zeta type

Gene

Prkcz

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei281 – 2811ATPPROSITE-ProRule annotation
    Active sitei376 – 3761Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri130 – 18051Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi258 – 2669ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. potassium channel regulator activity Source: Ensembl
    3. protein binding Source: UniProtKB
    4. protein kinase activity Source: MGI
    5. protein kinase C activity Source: UniProtKB-EC
    6. protein serine/threonine kinase activity Source: UniProtKB
    7. zinc ion binding Source: InterPro

    GO - Biological processi

    1. actin cytoskeleton reorganization Source: Ensembl
    2. activation of phospholipase D activity Source: Ensembl
    3. activation of protein kinase B activity Source: Ensembl
    4. cell migration Source: Ensembl
    5. establishment of cell polarity Source: UniProtKB
    6. inflammatory response Source: UniProtKB-KW
    7. insulin receptor signaling pathway Source: Ensembl
    8. long-term memory Source: Ensembl
    9. long-term synaptic potentiation Source: UniProtKB
    10. membrane hyperpolarization Source: Ensembl
    11. microtubule cytoskeleton organization Source: MGI
    12. negative regulation of apoptotic process Source: Ensembl
    13. negative regulation of hydrolase activity Source: Ensembl
    14. negative regulation of insulin receptor signaling pathway Source: Ensembl
    15. negative regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
    16. negative regulation of protein complex assembly Source: Ensembl
    17. neuron projection extension Source: MGI
    18. peptidyl-serine phosphorylation Source: Ensembl
    19. positive regulation of cell-matrix adhesion Source: Ensembl
    20. positive regulation of cell proliferation Source: Ensembl
    21. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    22. positive regulation of excitatory postsynaptic membrane potential Source: UniProtKB
    23. positive regulation of glucose import Source: Ensembl
    24. positive regulation of insulin receptor signaling pathway Source: UniProtKB
    25. positive regulation of interleukin-10 secretion Source: UniProtKB
    26. positive regulation of interleukin-13 secretion Source: UniProtKB
    27. positive regulation of interleukin-4 production Source: UniProtKB
    28. positive regulation of interleukin-5 secretion Source: UniProtKB
    29. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    30. positive regulation of T-helper 2 cell cytokine production Source: UniProtKB
    31. positive regulation of T-helper 2 cell differentiation Source: UniProtKB
    32. protein heterooligomerization Source: Ensembl
    33. protein kinase C signaling Source: Ensembl
    34. protein localization to plasma membrane Source: MGI
    35. protein phosphorylation Source: MGI
    36. vesicle transport along microtubule Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Inflammatory response

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDAi2.7.11.13. 3474.
    ReactomeiREACT_196549. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
    REACT_220092. GPVI-mediated activation cascade.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein kinase C zeta type (EC:2.7.11.13)
    Alternative name(s):
    nPKC-zeta
    Gene namesi
    Name:Prkcz
    Synonyms:Pkcz
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:97602. Prkcz.

    Subcellular locationi

    Cytoplasm By similarity. Endosome By similarity. Cell junction By similarity
    Note: In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction By similarity.By similarity

    GO - Cellular componenti

    1. apical cortex Source: MGI
    2. apical plasma membrane Source: MGI
    3. axon hillock Source: MGI
    4. cell-cell junction Source: UniProtKB
    5. cell cortex Source: MGI
    6. cell leading edge Source: Ensembl
    7. cytoplasm Source: MGI
    8. cytosol Source: Ensembl
    9. endosome Source: UniProtKB-SubCell
    10. membrane raft Source: Ensembl
    11. microtubule organizing center Source: MGI
    12. myelin sheath abaxonal region Source: BHF-UCL
    13. nuclear envelope Source: MGI
    14. nuclear matrix Source: MGI
    15. nucleus Source: MGI
    16. perinuclear region of cytoplasm Source: Ensembl
    17. plasma membrane Source: MGI
    18. protein complex Source: MGI
    19. tight junction Source: MGI

    Keywords - Cellular componenti

    Cell junction, Cytoplasm, Endosome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 592592Protein kinase C zeta typePRO_0000055702Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei410 – 4101Phosphothreonine; by PDPK1 and PI3KBy similarity
    Modified residuei560 – 5601PhosphothreonineBy similarity

    Post-translational modificationi

    CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ02956.
    PaxDbiQ02956.
    PRIDEiQ02956.

    PTM databases

    PhosphoSiteiQ02956.

    Expressioni

    Gene expression databases

    ArrayExpressiQ02956.
    BgeeiQ02956.
    CleanExiMM_PRKCZ.
    GenevestigatoriQ02956.

    Interactioni

    Subunit structurei

    Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 By similarity. Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDPK1 (via N-terminal region) By similarity.By similarity

    Protein-protein interaction databases

    BioGridi202203. 10 interactions.
    IntActiQ02956. 3 interactions.
    MINTiMINT-98101.

    Structurei

    3D structure databases

    ProteinModelPortaliQ02956.
    SMRiQ02956. Positions 13-182, 184-584.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini15 – 9884OPRAdd
    BLAST
    Domaini252 – 518267Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini519 – 59072AGC-kinase C-terminalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni79 – 14567Interaction with SQSTM1By similarityAdd
    BLAST

    Domaini

    The C1 domain does not bind the diacylglycerol (DAG).
    The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B.By similarity

    Sequence similaritiesi

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 1 OPR domain.Curated
    Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri130 – 18051Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117322.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiA2AD76.
    KOiK06069.
    OMAiRCHVLVP.
    OrthoDBiEOG7HF1J3.
    TreeFamiTF102004.

    Family and domain databases

    InterProiIPR000961. AGC-kinase_C.
    IPR020454. DAG/PE-bd.
    IPR011009. Kinase-like_dom.
    IPR000270. OPR_PB1.
    IPR012233. PKC_zeta.
    IPR017892. Pkinase_C.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PANTHERiPTHR24357:SF60. PTHR24357:SF60. 1 hit.
    PfamiPF00130. C1_1. 1 hit.
    PF00564. PB1. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000554. PKC_zeta. 1 hit.
    PRINTSiPR00008. DAGPEDOMAIN.
    SMARTiSM00109. C1. 1 hit.
    SM00666. PB1. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS00479. ZF_DAG_PE_1. 1 hit.
    PS50081. ZF_DAG_PE_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q02956-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDAMTTFKDL CEEVRDMCGL    50
    HQQHPLTLKW VDSEGDPCTV SSQMELEEAF RLVCQGRDEV LIIHVFPSIP 100
    EQPGMPCPGE DKSIYRRGAR RWRKLYRANG HLFQAKRFNR GAYCGQCSER 150
    IWGLSRQGYR CINCKLLVHK RCHVLVPLTC RRHMDSVMPS QEPPVDDKND 200
    GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG IKISQGLGLQ 250
    DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE 300
    KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE 350
    EHARFYAAEI CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE 400
    GLGPGDTTST FCGTPNYIAP EILRGEEYGF SVDWWALGVL MFEMMAGRSP 450
    FDIITDNPDM NTEDYLFQVI LEKPIRIPRF LSVKASHVLK GFLNKDPKER 500
    LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT DDYGLDNFDT 550
    QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV 592
    Length:592
    Mass (Da):67,682
    Last modified:July 27, 2011 - v2
    Checksum:i690AD891C25BC311
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti197 – 1971D → G in AAA39983. (PubMed:1487145)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M94632 mRNA. Translation: AAA39983.1.
    AL670413, AL670227 Genomic DNA. Translation: CAM20048.1.
    AL670227, AL670413 Genomic DNA. Translation: CAM20648.1.
    CH466594 Genomic DNA. Translation: EDL15000.1.
    CCDSiCCDS19026.1.
    PIRiJC1480.
    RefSeqiNP_032886.2. NM_008860.3.
    UniGeneiMm.28561.

    Genome annotation databases

    EnsembliENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053.
    GeneIDi18762.
    KEGGimmu:18762.
    UCSCiuc008wdc.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M94632 mRNA. Translation: AAA39983.1 .
    AL670413 , AL670227 Genomic DNA. Translation: CAM20048.1 .
    AL670227 , AL670413 Genomic DNA. Translation: CAM20648.1 .
    CH466594 Genomic DNA. Translation: EDL15000.1 .
    CCDSi CCDS19026.1.
    PIRi JC1480.
    RefSeqi NP_032886.2. NM_008860.3.
    UniGenei Mm.28561.

    3D structure databases

    ProteinModelPortali Q02956.
    SMRi Q02956. Positions 13-182, 184-584.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202203. 10 interactions.
    IntActi Q02956. 3 interactions.
    MINTi MINT-98101.

    PTM databases

    PhosphoSitei Q02956.

    Proteomic databases

    MaxQBi Q02956.
    PaxDbi Q02956.
    PRIDEi Q02956.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000030922 ; ENSMUSP00000030922 ; ENSMUSG00000029053 .
    GeneIDi 18762.
    KEGGi mmu:18762.
    UCSCi uc008wdc.1. mouse.

    Organism-specific databases

    CTDi 5590.
    MGIi MGI:97602. Prkcz.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117322.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    InParanoidi A2AD76.
    KOi K06069.
    OMAi RCHVLVP.
    OrthoDBi EOG7HF1J3.
    TreeFami TF102004.

    Enzyme and pathway databases

    BRENDAi 2.7.11.13. 3474.
    Reactomei REACT_196549. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
    REACT_220092. GPVI-mediated activation cascade.

    Miscellaneous databases

    NextBioi 294953.
    PROi Q02956.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q02956.
    Bgeei Q02956.
    CleanExi MM_PRKCZ.
    Genevestigatori Q02956.

    Family and domain databases

    InterProi IPR000961. AGC-kinase_C.
    IPR020454. DAG/PE-bd.
    IPR011009. Kinase-like_dom.
    IPR000270. OPR_PB1.
    IPR012233. PKC_zeta.
    IPR017892. Pkinase_C.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    PANTHERi PTHR24357:SF60. PTHR24357:SF60. 1 hit.
    Pfami PF00130. C1_1. 1 hit.
    PF00564. PB1. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000554. PKC_zeta. 1 hit.
    PRINTSi PR00008. DAGPEDOMAIN.
    SMARTi SM00109. C1. 1 hit.
    SM00666. PB1. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS00479. ZF_DAG_PE_1. 1 hit.
    PS50081. ZF_DAG_PE_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The cDNA sequence, expression pattern and protein characteristics of mouse protein kinase C-zeta."
      Goodnight J., Kazanietz M.G., Blumberg P.M., Mushinski F.J., Mischak H.
      Gene 122:305-311(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42."
      Joberty G., Petersen C., Gao L., Macara I.G.
      Nat. Cell Biol. 2:531-539(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PARD6B.
      Tissue: Embryo.
    5. Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
    6. "Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling."
      Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X., Prinjha R.K.
      , Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A., Cheng X., Gozani O.
      Nat. Immunol. 12:29-36(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiKPCZ_MOUSE
    AccessioniPrimary (citable) accession number: Q02956
    Secondary accession number(s): A2AD76
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 154 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3